title: STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes and the ER.
abstract: Inter-organelle membrane contacts sites (MCSs) are specific subcellular regions favoring the exchange of metabolites and information. We investigated the potential role of the late-endosomal membrane-anchored proteins StAR related lipid transfer domain-3 (STARD3) and STARD3 N-terminal like (STARD3NL) in the formation of MCSs involving late-endosomes (LEs). We demonstrate that both STARD3 and STARD3NL create MCSs between LEs and the endoplasmic reticulum (ER). STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. Together, they form an LE-ER tethering complex allowing heterologous membrane apposition. This LE-ER tethering complex affects organelle dynamics by altering the formation of endosomal tubules. An in situ proximity ligation assay between STARD3, STARD3NL and VAP proteins identified endogenous LE-ER MCS. Thus, we report here the identification of proteins involved in inter-organellar interaction.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Functional Genomics and Cancer Department, 1 rue Laurent Fries, Illkirch, 67404, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Alpy
authors.forename: Adrien
authors.initials: A
authors.lastname: Rousseau
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schwab
authors.forename: François
authors.initials: F
authors.lastname: Legueux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stoll
authors.forename: Corinne
authors.initials: C
authors.lastname: Wendling
authors.forename: Coralie
authors.initials: C
authors.lastname: Spiegelhalter
authors.forename: Pascal
authors.initials: P
authors.lastname: Kessler
authors.forename: Carole
authors.initials: C
authors.lastname: Mathelin
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Rio
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Levine
authors.forename: Catherine
authors.initials: C
authors.lastname: Tomasetto
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; C105684:STARD3 protein, human; C471300:STARD3NL protein, human; C114051:VAPA protein, human; D033921:Vesicular Transport Proteins
keywords: Endoplasmic reticulum; Endosome; MENTAL domain; MENTHO; MLN64; Membrane contact site; START domain